ANAPHYLAXIS Oh' ALLERGY 201 



there is also a decrease in antifennont wliich permits proteolysis of the animal's 

 own i)r()toins. As a result, there is to l)e founrl an increase in noncoaKiilable 

 nitrofjicn and ainino-acids of the hlood, and a decrease in sorinn proteases. "The 

 acute intoxication is hrouglit al)out by the cleavage of serum jjroteins throiiRh the 

 pci)tone sta}j;e l)y a non-specific protease. The specihc elements lie in the rapid 

 mobilization of this ferment and tlie colloidal serum changes which bring about 

 the change in antifcrment titer." 



As a result of extensive studies, Novy and DeKruif have developed ideas con- 

 cerning the nature of an:ii)hylaxis quite different from those ordinarily held.*^ 

 lM)ll()wing the observations of Bordet, and otliers, that incubation of fresh normal 

 serum with agar renders it capable of producing symptoms resembling those of 

 anajihylaxis, they have found reason to believe that the effects of bacteria may also 

 depend on similar phenomena, rather than on hypothetical endotoxins. As little as 

 9 mg. of agar may produce fatal intoxication if injected in a suitable physical state 

 intravenously into a guinea-pig. As perfectly dissolved 'VA'itte peptone or even 

 distilled water also produce anaphylatoxin when mixed with serum, it seems improb- 

 able that the anaphylatoxin formation depends on surface phenomena. Apparently 

 anaphylatoxin formation is closely a.ssociated with the coagulation of the blood, 

 which becomes highly toxic in the early stages of clot formation. Xo evidence 

 could be found of protein cleavage or enz5mie action during the formation of ana- 

 phylatoxin. It is thought that in specific anaphylaxis the substance that induces 

 the formation of anaphylatoxin is formed by the interaction of the antigen with 

 the antibody. The process of anaphylatoxin formation parallels closely that of 

 fibrin formation, to which it may be related. Anaphylatoxin is believed to be not 

 a proteose but a larger molecular complex than serum albumin, possessing certain 

 globulin characteristics. It is associated with the euglobulin fraction of the 

 , serum.** 



These and many other observations in the literature support the idea that a 

 change in the degree of dispersion of the blood colloids may be the fundamental 

 matter in anaphylaxis.*' 



The Anaphylactic Antibody (Anaphylactin). — That anaphylaxis, 

 like other immunity reactions, depends upon the presence of specific 

 antibodies in the blood of the sensitized animal, is shown by the pro- 

 duction of passive anaphylaxis in normal animals, by injecting into 

 them a few cubic centimeters of blood or serum from a sensitized ani- 

 mal. Such animals become sensitive in a few hours to the specific 

 antigen, no matter what species of animal furnishes the serum, show- 

 ing that various anaphylactins can unite with the same complement, 

 although strongly specific as to the antigen. In active sensitization 

 the anaphylactin appears in the blood in appreciable quantities about 

 eight days after the sensitizing injection, increases to a maximum 

 between the 15th and 30th days, and then very slowly decreases. The 

 reaction of antibody and antigen is strictly quantitative, as with all 

 amboceptor reactions. The amount of antibody developed seems to 

 be limited, for after a sensitized animal is given a sub-lethal intoxicating 

 dose of protein it may be no longer sensitive to this protein, and this 

 refractory or anti-anaphylactic condition persists for three weeks or 

 more. It has been demonstrated especialh' conclusively by Weil and 

 Coca,®" that this refractory condition is, as Friedberger suggested, de- 



*Mour. Infect. Dis., 1917 (20); recapitulation in Jour. Amer. Med. Assoc, 

 1917 (68), 1524. 



"DeKruif and Eggerth, Jour. Infect. Dis., 1919 (24), 505. They state also 

 that in primarilv toxic sera the toxic element is associated wdth the pseudoglobulin. 



" See Kritciiewskv, Jour. Infect. Dis., 1918 (22), 101. 



60 Zeit. Immunitat., 1913 (17), 141. 



